Steroid During Heart Surgery Has No CV Benefit

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Giving high-dose dexamethasone as a prophylactic during heart surgery didn't reduce cardiovascular events, but it may diminish respiratory failure and infections.

Note that dexamethasone did appear to lessen both the duration of postoperative respiratory failure and infection.

Giving high-dose dexamethasone as a prophylactic during heart surgery didn't reduce cardiovascular events, but it may diminish respiratory failure and infections, researchers found.

In a randomized, controlled trial, there was no significant difference in a primary composite endpoint of adverse cardiovascular events between those given a high dose of the steroid and those given placebo (P=0.07), Jan Dieleman, MD, of the University Medical Center Utrecht in the Netherlands, and colleagues reported.

But dexamethasone did appear to lessen both the duration of postoperative respiratory failure and infection (P=0.02 and P<0.001), they wrote in the Nov. 7 issue of the Journal of the American Medical Association.

"No significant benefit from dexamethasone treatment was observed on the composite primary endpoint, which was largely cardiovascular," they wrote. "However, further exploration of the study data suggests a consistent pattern of improved pulmonary condition ... which was accompanied by earlier discharge from both the ICU and the hospital."

Dieleman told MedPage Today in an email that the study "has certainly not provided a definitive answer to this long-standing question, which is what many people had been hoping for. It might have even brought up more questions."

But the study should allay some concerns, he said, given that there was "no real clinically relevant downside to the use of dexamethasone in terms of possible adverse effects. Moreover, routine dexamethasone use might even lead to some respiratory benefit in the postoperative period, although these benefits need to be confirmed in a study that is specifically designed to look at respiratory outcomes."

After cardiopulmonary bypass, many patients experience a systemic inflammatory response that involves fever and organ dysfunction. Some clinicians give corticosteroids during heart surgery to mitigate the anticipated inflammation -- the practice is more common in European centers than in U.S. centers -- but there are concerns about adverse effects including poor blood sugar control, poor wound healing, and gastrointestinal bleeding.

There is also no consistent evidence supporting the use of prophylactic high-dose steroids in this setting.

So Dieleman and colleagues conducted the multicenter, randomized, double-blind, placebo-controlled dexamethasone for cardiac surgery (DECS) trial of 4,494 patients who had heart surgery with cardiopulmonary bypass at eight cardiac surgical centers in the Netherlands between Apr. 13, 2006 and Nov. 23, 2011.

Patients received either a single intra-operative dose of dexamethasone (1 mg/kg) or placebo; the primary outcome was a composite of death, MI, stroke, renal failure, or respiratory failure within 30 days.

Overall, 7% of patients in the dexamethasone group and 8.5% of those in the placebo group reached the primary endpoint -- a finding that trended significant but had a confidence interval straddling 1 (RR 0.83, 95% CI 0.67 to 1.01, P=0.07).

In an exploratory analysis of individual endpoint components, rates of death, MI, stroke, and renal failure were similar in both groups -- but respiratory failure was significantly reduced in the dexamethasone group (3% versus 4.3%, RR 0.69, 95% CI 0.51 to 0.94, P=0.02).

The steroid also lowered the risk of postop infection compared with placebo (9.5% versus 14.8%, RR 0.64 95% CI 0.54 to 0.75, P<0.001), an effect that was primarily related to a lower incidence of pneumonia in the dexamethasone group, the researchers said.

This finding was unexpected "and contrary to existing knowledge that corticosteroids increase the risk of infections," although that tends to be related to chronic corticosteroid use, they noted.

Dexamethasone also reduced the mean wean time from the mechanical ventilator (11 hours versus 14.3 hours, P<0.001) and the mean time to discharge from the ICU (34.2 hours versus 43.6 hours, P<0.001).

Both of these measures had similar median values, but that reflected the higher proportion of patients requiring prolonged ventilation times and longer ICU stays in the placebo group, the researchers wrote.

In pre-planned subgroup analyses, Dieleman and colleagues found an age-dependent effect of dexamethasone on the primary endpoint, as patients under 65 given the steroid had a significantly lower risk of the primary endpoint (RR 0.65, 95% CI 0.44 to 0.96, P=0.03), which wasn't significant for patients ages 80 and up.

Dieleman and colleagues presented the results of a post-hoc substudy of the DECS trial at the American Society of Anesthesiologists meeting in Washington last month, which found that dexamethasone also significantly reduced the amount of blood products that had to be transfused during surgery.

The study was limited because European centers use dexamethasone in this setting, but when it's done in the states, methylprednisolone is preferred. The latter is being evaluated in the Steroids in Cardiac Surgery (SIRS) trial.

Dieleman said the DECS study "has certainly provided a good direction for further studies into the clinical effects of corticosteroids in cardiac surgery" and that a prospective study focusing on pulmonary outcomes is a "logical next step."

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